This application addresses broad Challenge Area (04) Clinical Research, and specific Challenge Topic 04-HL-104: Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions. We request funding to support one additional cycle of observational follow-up of Women's Health Study (WHS) participants, to ascertain and validate cardiovascular disease (CVD) and cancer endpoints among cohort subjects, in order to retain jobs, support the research of junior faculty, and have increased power to both continue and initiate the evaluation of clinically important questions. The WHS began in 1992 as a randomized trial of aspirin and vitamin E in the primary prevention of CVD and cancer among 39,876 female health professionals aged e45 years. Completed in 2004 after an average of 10 years of treatment and follow-up, the participants are now followed observationally, returning yearly endpoint and risk factor questionnaires. Morbidity follow-up is well over 90%;mortality follow-up virtually 100%;and review completed of about 90% of medical records for self-reported CVD and cancer endpoints. Thus, the WHS is an extraordinary resource for research in women, in that not only does it have extensive demographic, lifestyle and medical history risk factor data as well as CVD and cancer outcome data for over 39,000 women collected yearly over an average of 15 years, but it also has comprehensive plasma-based biomarker and genetic data (including whole genome scans) available on over 28,000 participants. However, our current NIH funding supporting the ascertainment and validation of both the cardiovascular and cancer endpoints (Women's Health Study: Continued Follow-up - CA047988), ends on 6/30/09 (our current NHLBI funding (HL080467) provides support only for genetic analyses, not for any endpoint ascertainment). While this funding will allow us to mail out the 2009 follow-up questionnaires in May as scheduled, we have NO funding to process these questionnaires, obtain participant consent for medical record review of self-reported endpoints, obtain medical records, or validate through our Endpoints Committee of physicians. Our competing renewal application was positively reviewed but did not receive a fundable score, and we are resubmitting the application in July, 2009. However, because of the timing of this resubmission and subsequent start date, we will have no funding for the entire 2009 cycle of endpoints, and because of this gap, we will not be able to continue the current WHS staffing and functions. The financial impact of this gap is substantial: without additional funding, we will need to lay off 5 FTE WHS staff members (the study coordinator, programmer, data manager, and two research assistants) and FTE support for three WHS research faculty will be substantially reduced. Moreover, the research impact of the WHS is substantially driven by the number of validated endpoints available to power the studies which depend upon its resources. Without additional follow-up, the resultant decrease in the number of validated endpoints will critically adversely impact the success of many ongoing investigations by WHS investigators, as well as ancillary studies and NIH-sponsored collaborations with other CVD, cancer and genomic investigators. Because of the aging of the cohort, this one additional cycle of follow-up will add new data from medical record review for an estimated 171 validated CVD and 327 validated cancer endpoints, increasing the statistical power available for many investigators to adequately evaluate specific research hypotheses of particular relevance to women. There are currently over 29 currently funded ancillary grants and 10 grants submitted and under NIH review requiring these updated endpoints. Letters of Support from 12 representative investigators whose studies are dependent on these endpoints from the WHS are included. The impact of the ascertainment and validation of WHS endpoints to date has been substantial, with over 230 publications and 35 completed ancillary studies. In addition to furthering scientific knowledge, funding of this proposal will fulfill the goal of the American Recovery and Reinvestment Act (ARRA) to create and retain jobs and boost the economy. If funded, this proposal will retain 5 staff positions in the Division of Preventive Medicine, Brigham and Women's Hospital, as well as partial support for three WHS faculty. The data generated will support the research efforts of more than 40 research faculty whose funded, submitted or about to be submitted ancillary research studies are dependent on these WHS data. Additional follow-up (and the resulting increase in the endpoints of interest) will, without question, maximize the impact of the Women's Health Study in continuing to contribute to the state of knowledge concerning CVD and cancer prevention in the understudied population of women. The Women's Health Study is an ongoing (since 1992) observational follow-up study of almost 40,000 participants from a completed trial, designed to add knowledge concerning prevention of cardiovascular disease and cancer in women. Funding will allow the ascertainment and validation of one cycle of endpoints, allowing increased power to evaluate hypotheses, the ability to retain 5 staff members, and the ability for the study to continue to be a source of data for ongoing and planned research of over 40 faculty.